Many diseases, such as cancer, are often pernicious and very aggressive. Treatment is often complicated by the fact that some of the most effective treatment methods can have a deleterious impact on surrounding healthy tissue and cells. As a result, more recent efforts have moved toward therapies which attempt to target only unhealthy cells and thereby minimize the impact on healthy cells.
Hyperthermia is one such approach to cancer therapy. Hyperthermia associated with radiotherapy or chemotherapy is a method for cancer treatment in which body tissue is exposed to high temperatures, up to 113° F. (45° C.). Although the molecular mechanisms of this process are not well understood, hyperthermia exhibits various anti-tumor effects, including damage of tumor cell structure and vasculature. Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. By killing cancer cells and damaging proteins and structures within cancer cells, hyperthermia may shrink tumors.
Hyperthermia is almost always used with other forms of cancer therapy, such as radiation therapy and chemotherapy. Hyperthermia may make some cancer cells more sensitive to radiation or harm other cancer cells that radiation cannot damage. When hyperthermia and radiation therapy are combined, they are often given within an hour of each other. Hyperthermia may also enhance the effects of certain anticancer drugs.
Numerous clinical trials have studied hyperthermia in combination with radiation therapy and/or chemotherapy. These studies have focused on the treatment of many types of cancer, including sarcoma, melanoma, and cancers of the head and neck, brain, lung, esophagus, breast, bladder, rectum, liver, appendix, cervix, and peritoneal lining (mesothelioma). Many of these studies, but not all, have shown a significant reduction in tumor size when hyperthermia is combined with other treatments. However, not all of these studies have shown increased survival in patients receiving the combined treatments.
In local hyperthermia, heat is applied to a small area, such as a tumor, using various techniques that deliver energy to heat the tumor. Different types of energy may be used to apply heat, including microwave, radio-frequency, and ultrasound energy. Depending on the tumor location, there are several approaches to local hyperthermia.
External approaches are used to treat tumors that are located in or just below the skin. External applicators are positioned around or near the appropriate region, and energy is focused on the tumor to raise its temperature.
Intraluminal or endocavitary methods may be used to treat tumors within or near body cavities, such as the esophagus or rectum. Probes are placed inside the cavity and inserted into the tumor to deliver energy and thereby heat the area directly.
Interstitial techniques are used to treat tumors deep within the body, such as brain tumors. These techniques allow the tumor to be heated to higher temperatures than external techniques. Under anesthesia, probes or needles are inserted into the tumor. Imaging techniques, such as ultrasound, may be used to make sure the probe is properly positioned within the tumor. The heat source is then inserted into the probe. Radiofrequency ablation (RFA) is a type of interstitial hyperthermia that uses radio waves to heat and kill cancer cells.
In regional hyperthermia, various approaches may be used to heat large areas of tissue, such as a body cavity, organ, or limb.
Deep tissue approaches may be used to treat cancers within the body, such as cervical or bladder cancer. External applicators are positioned around the body cavity or organ to be treated, and microwave or radiofrequency (RF) energy is focused on the area to raise its temperature.
Regional perfusion techniques may be used to treat cancers in the arms and legs, such as melanoma, or cancer in some organs, such as the liver or lung. In this procedure, some of the patient's blood is removed, heated, and then pumped (perfused) back into the limb or organ. Anticancer drugs are commonly given during this treatment.
Continuous hyperthermic peritoneal perfusion (CHPP) is a technique used to treat cancers within the peritoneal cavity (the space within the abdomen that contains the intestines, stomach, and liver), including primary peritoneal mesothelioma and stomach cancer. During surgery, heated anticancer drugs flow from a warming device through the peritoneal cavity. The peritoneal cavity temperature typically reaches about 106-108° F. (about 41.1-42.2° C.).
Whole-body hyperthermia is used to treat metastatic cancer that has spread throughout the body. This may be accomplished by several techniques that typically raise the body temperature to about 107-108° F. (about 41.7-42.2° C.), including the use of thermal chambers (similar to large incubators) or hot water blankets.
Cancer cells are more sensitive to higher body temperatures than are normal cells. Hyperthermia destroys cancer cells by raising the tumor temperature to a “high fever” range, similar to the way the body uses fever naturally when combating other forms of disease. Because the body's means of dissipating heat is through cooling from blood circulation, sluggish or irregular blood flow leaves cancerous tumor cells vulnerable to destruction at elevated temperatures that are safe for surrounding healthy tissues with normal, efficient blood cooling systems.
Although not wishing to be bound by theory, scientists tend to attribute the destruction of cancer cells at hyperthermic temperatures to damage in the plasma membrane, the cytoskeleton, and the cell nucleus. Cancer cells are vulnerable to hyperthermia therapy particularly due to their high acidity caused by the inability to properly expel waste created by anaerobic metabolism. Hyperthermia attacks acidic cells, disrupting the stability of cellular proteins and killing them.
Radiofrequency hyperthermia is a non-ionizing form of radiation therapy that can substantially improve results from cancer treatment. For chemotherapy drugs that depend on blood transport for delivery, hyperthermia used in combination with chemotherapy (thermo-chemotherapy) enhances blood flow in tumor tissues, increasing the uptake of chemotherapy drugs in tumor membranes. Hyperthermia also induces disassembly of the cytoskeleton, which enlarges the tumor pores for easier drug entry. Once the drug is delivered, hyperthermic temperatures may be used as a drug activator, accelerating chemical reactions through heat and drawing essential oxygen molecules to tumor tissue for chemical reaction with the drug.
Several therapies are associated with non-ionizing RF hyperthermic therapy. One is RF ablation, where direct radio-stimulation contact of cancerous tissues creates a local heat intense enough to kill neoplastic cells. Another RF approach is to direct RF at nanoparticle and microparticle targets localized in the tumor site. These nano and micro spheres may be affixed with antibodies to focus the delivery of the particle to the tumor site that then becomes the target of RF stimulation to directly deliver heat to the local tissue. Still another approach is to combine the separate actions of chemotherapeutic agents with tissue hyperthermia.
Polymers are used extensively in the preparation of biomaterials. Certain biomaterials used in the field include biocompatible and/or bioabsorbable synthetic polymers that are composed of monomers having different affinities for water. For example, in certain polymers formed from glycerol and a diacid, the glycerol may be water soluble while the diacid is nearly insoluble. Thus, when biomaterials including these compounds are prepared, the process for such preparation may simply include adding the monomers neatly to a vessel and allowing them to react directly. Such processes may be problematic because the polymerization reaction may be difficult to control and modify. The products of such reactions may have inconsistent properties between batches, resulting in biomaterials that may fail to perform consistently.
A conventional process of forming poly(glycerol sebacate) (PGS) via an anhydrous polycondensation reaction includes reacting glycerol and sebacic acid at about 248° F. (about 120° C.) for about 24 hours followed by about 48 hours at about 248° F. (about 120° C.) and a pressure of about 1 Torr or less to yield a colorless elastomer. The length of time for this synthesis and the high polydispersity of the PGS product limit the commercial viability of the PGS product.